Efficacy and safety of 5-Hydroxytryptophan on levodopa-induced motor complications in Parkinson's disease: A preliminary finding.

BACKGROUND AND PURPOSE: Several studies have indicated that altered serotonergic neurotransmission may contribute to the motor features commonly associated with Parkinson's disease (PD) drug treatment such as levodopa-induced dyskinesias (LIDs). 5-Hydroxytryptophan (5-HTP) is the immediate precursor of serotonin. We have recently demonstrated that 5-HTP produces significant antidyskinetic effects in a rat model of PD. To date, there has been inconsistent research on the use of 5-HTP in PD. The purpose of this study was to compare the effects of 5-HTP versus placebo on levodopa-induced motor complications in PD patients. MATERIAL AND METHODS: A single-center, randomized, double-blind placebo-controlled cross-over study was performed. A total of 12 PD patients were diagnosed with LIDs and motor fluctuactions and subsequently were randomized to intervention; 11 subjects completed the entire 16-week protocol. Patients received placebo or 50 mg of 5-HTP daily in a cross-over design over a period of 4 weeks. For the assessment of efficacy on the motor functions and motor complications, the UPDRS (parts III and IV), Unified Dyskinesia Rating Scale (UDysRS), Wearing-Off Questionnaire (WOQ-19) and the self-reported 24-h home dyskinesia diaries were obtained at baseline and weeks 4, 8, 12 and 16 (T-end). RESULTS: Repeated measures analysis revealed a significant improvement of LIDs during the 50 mg 5-HTP treatment as assessed by the UDysRS and UPDRS-IV scores. CONCLUSIONS: This study provides preliminary evidence of clinical benefit of 5-HTP against LIDs in PD. Larger studies with a longer treatment duration and a wider range of doses are warranted to corroborate these findings.

C9ORF72 Intermediate Repeat Expansion in a Patient With Psychiatric Disorders and Progressive Cerebellar Ataxia.

INTRODUCTION: Large expansions of the noncoding GGGGCC repeat (more than 30) in the first intron of the C9ORF72 gene have been demonstrated to cause amyotrophic lateral sclerosis and frontotemporal dementia. Recent papers have investigated the possible pathogenic role and associated clinical phenotypes of hexanucleotide expansions with intermediate repeat lengths ranging between 20 and 29 repeats. CASE REPORT: We report a case of a 71-year-old Sardinian female patient with a long history of psychiatric disorders such as mixed anxiety-depressive disorder associated with somatization disorder and histrionic personality who developed a slowly progressive cerebellar syndrome, mild cognitive impairment, pyramidal signs, and rapid eye movement sleep behavior disorder with imaging abnormalities on the DaTSCAN single-photon emission computed tomography indicating an alteration in the presynaptic dopaminergic system. The patient was found to have intermediate C9ORF72 repeat expansions. CONCLUSIONS: Early psychiatric presentations are a recurrent phenotypic manifestation of C9ORF72 expansions. In our patient, the intermediate C9ORF72 repeat expansion may have a pathogenic role in the cooccurrence of psychiatric and sleep disorders, cognitive dysfunctions, pyramidal system involvement, and late-onset cerebellar ataxia. This observation widens the spectrum of neurodegenerative conditions linked to C9ORF72 mutations.

C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson's disease complicated by psychosis or dementia in a Sardinian population.

The hexanucleotide repeat expansion GGGGCC in the C9ORF72 gene larger than 30 repeats has been identified as a major genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent papers investigated the possible pathogenic role and associated clinical phenotypes of intermediate C9ORF72 repeat expansion ranging between 20 and 30 repeats. Some studies suggested its pathogenicity for typical Parkinson's disease (PD), atypical parkinsonian syndromes, FTD with/without parkinsonism, and ALS with/without parkinsonism or with/without dementia. In our study, we aimed to screen patients affected by atypical parkinsonian syndromes or PD complicated by psychosis or dementia for the presence of C9ORF72 repeat expansions, and in unrelated age- and sex-matched healthy controls. Consecutive unrelated patients with atypical parkinsonian syndromes and patients with PD complicated by psychosis or dementia were included in this study. Atypical parkinsonian syndromes were further divided into two groups: one with patients who met the criteria for the classic forms of atypical parkinsonism [multiple system atrophy (MSA), Lewy body disease (LBD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] ;and patients who did not meet the above criteria, named non-classical atypical parkinsonism with or without dementia. Ninety-two unrelated patients (48 men, 44 women) were enrolled. None of the patients was found to be carriers of C9ORF72 repeat expansions with more than 30 repeats. Intermediate 20-30 repeat expansions were detected in four female patients (4.3 %). Three of them presented clinical features of atypical parkinsonian syndromes, two with non-classical atypical parkinsonism and dementia FTD-like, and one with non-classical atypical parkinsonism without dementia. The other patient presented clinical features of typical PD complicated by psychosis. Among 121 control subjects, none presented long or short expansion for the C9ORF72 gene. Our findings seem to support the hypothesis that the hexanucleotide expansions of C9ORF72 gene with intermediate repetitions between 20 and 29 repetitions could be associated with typical PD with psychosis or dementia and atypical parkinsonisms with dementia (non-classical atypical parkinsonism with dementia FTD-like) or without dementia (non-classical atypical parkinsonism upper MND-like), although the causal relationship is still unclear. In these latter patients, parkinsonism, more or less levodopa responsive, constituted the symptomatological central core at onset.